Sulphur trioxide

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Literature study, comparable to OECD 414

Data source

Reference

Reference Type:

publication

Title:

Embryotoxicity of inhaled sulfuric acid aerosol in mice and rabbits

Author:

Murray FJ, Schwetz BA, Nitschke KD, Crawford AA, Quast JF & Staples RE

Year:

1979

Bibliographic source:

J Environ Sci Health (Part C) 13(3): 251-66

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

Deviations:

yes

Remarks:

Number of exposure levels

Principles of method if other than guideline:

Sulphuric acid was tested by inhalation for embryotoxicity in mice according to a protocol similar to OECD guideline 414

GLP compliance:

no

Remarks:

Older, published study

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Sulphuric acid

EC Number:

231-639-5

EC Name:

Sulphuric acid

Cas Number:

7664-93-9

Molecular formula:

H2O4S

IUPAC Name:

sulfuric acid

Details on test material:

Aerosols were generated for each chamber by nebulising 2M sulphuric acid (95.7%)

Test animals

Species:

mouse

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure (if applicable):

whole body

Vehicle:

water

Analytical verification of doses or concentrations:

yes

Details on mating procedure:

Nulliparous female mice were pen-bred with fertile males of the same strain. The day on which a vaginal plug was observed in mice was considered day zero of gestation.

Duration of treatment / exposure:

7 hours/day: Day 6-15 of gestation

Frequency of treatment:

Daily

Duration of test:

Day 18 of gestation

No. of animals per sex per dose:

35 (with controls)

Control animals:

yes

Results and discussion

Results: maternal animals

Effect levels (maternal animals)

1

Dose descriptor:

LOAEC

Effect level:

19.3 mg/m³ air (analytical)

Basis for effect level:

other: maternal toxicity

2

Dose descriptor:

NOAEC

Effect level:

5.7 mg/m³ air (analytical)

Basis for effect level:

other: maternal toxicity

3

Dose descriptor:

NOAEC

Effect level:

19.3 mg/m³ air (analytical)

Basis for effect level:

other: developmental toxicity

Results (fetuses)

Effect levels (fetuses)

Dose descriptor:

NOAEC

Effect level:

19.3 mg/m³ air (analytical)

Basis for effect level:

other: teratogenicity

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Any other information on results incl. tables

Inhalation of 5 or 20 mg sulphuric acid/m3 did cause any signs of toxicity.  The incidence of pregnancy was not significantly altered among the mice. Bodyweight gain of exposed mice was not significantly affected but a significant decrease in the amount of food consumed during the first few days of exposure was observed at 20 mg/m3. The liver weight of dams was significantly decreased in mice exposed to 20 mg/m3 compared to controls. No evidence of toxicity that could be attributed to sulphuric acid was observed in the respiratory tract of mice (nasal turbinates, trachea and lungs).  The mean numbers of implants/dam, live foetuses/litter, or resorptions/litter were not significantly altered by exposures.  No significant effect on foetal sex ratio was seen.  Mean weights and lengths of the offspring of mice exposed to sulphuric acid were not significantly different from their respective control values.  The offspring of mice exposed to sulphuric acid did not have a significantly higher incidence of malformations than controls.  Inhalation of sulphuric acid did not increase the incidence of minor skeletal variants among the offspring of exposed mice.

Applicant's summary and conclusion

Conclusions:

No evidence of teratogenicity, embryotoxicity, foetotoxicity or developmental toxicity was seen under the conditions of this study, at exposure levels sufficient to cause mild maternal toxicity.

Executive summary:

Mated female mice were exposed (whole body) to atmospheres containing aerosols of sulphuric acid at 0, 5.7 mg/m3 (MMAD 1.6 um) or 19.3 mg/m3 (MMAD 2.4 um) on Days 6 -15 of gestation (mice). Animals were sacrificed at Days 18 (mice). Evidence of mild toxicity was seen in maternal mice (reduced food consumption) at 20 mg/m3. No evidence of teratogenicity or developmental toxicity was seen.