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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
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: 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 and rabbits according to a protocol similar to OECD guideline 414
GLP compliance:
no
Remarks:
: older, published study
Limit test:
no

Test material

Constituent 1
Chemical structure
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:
other: Rabbit, mouse
Strain:
other: New Zealand White, CF-1

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. Nulliparous female rabbits were artificially inseminated. The day on which a vaginal plug was observed in mice or the day on which rabbits were artificially inseminated was considered day zero of gestation
Duration of treatment / exposure:
7 hours/day: Day 6-18 of gestation (rabbit), Day 6-15 of gestation (mouse)
Frequency of treatment:
Daily
Duration of test:
Day 29 of gestation (rabbit), Day 18 of gestation (mouse)
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0, 5, 20 mg/m3
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
0, 5.7, 19.3 mg/m3
Basis:
analytical conc.
No. of animals per sex per dose:
20 (rabbit); 35 (mouse) with 40 controls
Control animals:
yes

Results and discussion

Results: maternal animals

Effect levels (maternal animals)

open allclose all
Dose descriptor:
LOAEC
Remarks:
(mouse)
Effect level:
19.3 mg/m³ air (analytical)
Basis for effect level:
other: maternal toxicity
Dose descriptor:
NOAEC
Remarks:
(mouse)
Effect level:
5.7 mg/m³ air (analytical)
Basis for effect level:
other: maternal toxicity
Dose descriptor:
NOAEC
Remarks:
(mouse)
Effect level:
19.3 mg/m³ air (analytical)
Basis for effect level:
other: developmental toxicity
Dose descriptor:
LOAEC
Remarks:
(rabbit)
Effect level:
19.3 mg/m³ air (analytical)
Basis for effect level:
other: maternal toxicity
Dose descriptor:
NOAEC
Effect level:
5.7 mg/m³ air (analytical)
Basis for effect level:
other: maternal toxicity
Dose descriptor:
NOAEC
Effect level:
19.3 mg/m³ air (analytical)
Basis for effect level:
other: developmental toxicity

Results (fetuses)

Effect levels (fetuses)

open allclose all
Dose descriptor:
NOAEC
Remarks:
(mouse)
Effect level:
19.3 mg/m³ air (analytical)
Basis for effect level:
other: teratogenicity
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 and rabbits.  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.  In rabbits, a statistically significant decrease in maternal bodyweight gain was noted during the first few days of exposure to 20 mg/m3.  The liver weight of dams was unaltered by exposure to sulphuric acid in rabbits whereas it 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).  In rabbits, a trends toward a dose-related increase in the incidence of subacute rhinitis and tracheitis was noted.  The mean numbers of implants/dam, live foetuses/litter, or resorptions/litter were not significantly altered by exposures in both species.  No significant effect on foetal sex ratio was seen in either species.  Mean weights and lengths of the offspring of mice and rabbits exposed to sulphuric acid were not significantly different from their respective control values.  The offspring of mice and rabbits 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.  In rabbits, an increased incidence of small non-ossified areas in the skull bones (a minor variation) was the only statistically significant evidence of embryotoxicity observed among the offspring of rabbits exposed to 20 mg/m3.

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 and inseminated female rabbits 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) or on Days 6 -18 of gestation (rabbits). Animals were sacrificed at Days 18 (mice) or 29 of gestation (rabbits). Evidence of mild toxicity was seen in maternal mice (reduced food consumption) and rabbits (reduced weight gain, respiratory tract effects) were seen at 20 mg/m3. No evidence of teratogenicity or developmental toxicity was seen in either species.

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