Reaction mass of sulphuric acid, hydrogen peroxide and peroxomonosulphuric acid

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

no data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The reaction mass of sulphuric acid, hydrogen peroxide and peroxomonosulphuric acid is predominantly sulphuric acid (>80%). Although all constituents of the reaction mass contribute towards and are essential for the desired technical effects of the range, it is considered acceptable to read-across to data on sulphuric acid. This because significant toxicological effects are likely to be masked in the multi-constituent substance by its corrosive nature and so it considered appropriate to read across to the mean constituent, sulphuric acid, when considering reproductive and developmental toxicity.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
See read-across data matrix under 'Attached background material' below.

3. ANALOGUE APPROACH JUSTIFICATION
See read-across data matrix under 'Attached background material' below.

4. DATA MATRIX
See read-across data matrix under 'Attached background material' below.

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, C13(3): 251-266

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

Deviations:

not specified

GLP compliance:

no

Remarks:

Study pre-dates GLP

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:

Sulphuric acid

Test material form:

aerosol dispenser: not specified

Remarks:

migrated information: aerosol

Details on test material:

- Sulphuric acid (Lot number 627042; purity 95.7 %) was obtained from JT Baker Chemical Company, Phillipsburg, New Jersey.

Test animals

Species:

mouse

Strain:

CF-1

Details on test animals or test system and environmental conditions:

- Nulliparous CF-1 mice (Charles River, Portgage, Michigan) were housed in wire-mesh cages
- Animals were housed in rooms designed to control temperature at 21 °C.
- Humidity was maintained at 45 %
- A cycle of 12 h light and 12 h dark was maintained.
- Animals were given free access to commercial laboratory chow (Ralston Purina Company, St Louis, Missouri) and tap water.
- Mice were acclimated to the environment for at least two weeks prior to commencement of the study.

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure (if applicable):

whole body

Vehicle:

water

Details on exposure:

- Control animals were placed in chambers identical to those used for sulphuric acid exposure.
- Animals did not have access to food or water while in the exposure chambers.
- Exposures were conducted under dynamic airflow conditions in 4.3 m3 stainless steel and glass Rochester-type chambers.
- Chamber airflow was approximately 800 L/min.
- The aerosol was generated for each chamber by nebulising 2M sulphuric acid with a pneumatic atomising nozzle (Spraying System Company, Bellwood, Illinois)

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

- Sulphuric acid concentration in the exposure chambers was analysed three times per day throughout exposure with a column made of DOWEX 50W x 8 with a water eluent using a conductivity cell detector.
- Particle size of the aerosol was determined on four different exposure days using a particle size monitor (Royco instruments, Menlo park, California).
- The mean of the average time-weighted daily concentrations of sulphuric acid and the count median diameter of the sulphuric acid particles were recorded.

Details on mating procedure:

- 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 to be day zero of gestation.

Duration of treatment / exposure:

- Day 6 to day 15 of gestation.

Frequency of treatment:

- Exposure took place for 7 h per day

Duration of test:

- Length of normal pregnancy

No. of animals per sex per dose:

- 35 bred were mice exposed in each group.
- Forty bred mice acted as vehicle controls and were exposed to filtered room air.

Control animals:

yes, sham-exposed

Details on study design:

- Mice were sacrificed by carbon dioxide inhalation on day 18 of gestation.

Examinations

Maternal examinations:

- All animals were observed daily beginning on day 6 of gestation for indications of toxicity.
- Body weights were recorded on days 6, 8, 10, 16 and 18 of gestation.
- Consumption of food and water was measured at three day intervals.

Ovaries and uterine content:

- The uterus of each non-pregnant female was stained with a 10 % solution of sodium sulphide and examined for evidence of implantation sites.

Fetal examinations:

- The number and position of live, dead and resorbed foetuses was noted.
- The heads of mice examined internally were placed in Bouin's solution and examined by the razor-section technique.
- All foetuses were weighed, measured (crown-rump length), sexed, and examined for external alterations and cleft palate.
- One third of the foetuses from each litter were selected at random and immediately examined for evidence of soft tissue alterations by dissection under a stereo-microscope.
- All foetuses were cleared in KOH, stained with alizarin red-S and examinded for skeletal alterations.

Statistics:

- The Wilcoxon test as modified by Haseman and Hoel was used to evaluate the incidence of foetl alterations and resorptions.
- The litter was used as the experimental unit.
- Continuous data were analysed by one-way analysis of variance and Dunnett's test.
- The level of significance chosen for all cases was p < 0.05.

Historical control data:

- Several cases of exencephaly were noted among exposed mice. However, the incidence of this malformation in the experimental groups was not inconsistent with that seen among control groups in other studies conducted in the same laboratory.

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Details on maternal toxic effects:
- Inhalation of 5 mg/m3 or 20 mg/m3 sulphuric acid did not alter the appearance of dams.
- Compared to the control group, the incidence of pregnancy, as well as the proportion of pregnancies detected by sodium sulphide stain, was not significantly altered.
- Body weight gain of mice exposed to sulphuric acid was not significantly less than that of the control group.
- A significant decrease in the amount of food consumed during the first few days of exposure was observed at 20 mg/m3 but not at 5 mg/m3.
- At sacrifice, the liver weight (absolute and relative) of pregnant mice exposed to 20 mg/m3 was significantly less than that of the controls.
- Gross and microscopic examination of the nasal turbinates, trachea, and lungs of mice revealed no evidence of toxicity that could be attributed to sulphuric acid.

Effect levels (maternal animals)

Dose descriptor:

NOAEC

Effect level:

19.3 mg/m³ air (analytical)

Based on:

test mat.

Basis for effect level:

other: developmental toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
- Exposure of mice to sulphuric acid did not significantly alter the mean numbers of implants per dam, live foetuses per litter, or resorptions per litter.
- No significant effect on foetal sex ratio was seen in mice.
- Mean body weights and lengths of the offspring of mice exposed to sulphuric acid were not significantly different from the controls.
- Whether considered individually or collectively, offspring of mice exposed to sulphuric acid did not have significantly higher incidence of malformations than the controls.
- In the 20 mg/m3 group, two foetuses were conjoined ventrally through the head, neck and thoracic regions. One of the conjoined heads had exencephaly, ablepharis and cleft palate; the other head was micrognathic and lacked an oral opening. Although the occurrance of conjoined foetuses is extremely rare, one case was not considered sufficient evidence to conclude that sulphuric acid was teratogenic.
- Inhalation of sulphuric acid did not increase the incidence of minor skeletal variants among the offspring of exposed mice.

Effect levels (fetuses)

Dose descriptor:

NOAEC

Effect level:

19.3 mg/L air (analytical)

Based on:

test mat.

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

JUSTIFICATION FOR USE OF READ-ACROSS DATA

See comparison of overall physico-chemical and toxicity profiles for target and source chemicals in the data matrix (attached)

CONCENTRATION AND PARTICLE SIZE OF SULPHURIC ACID IN THE CHAMBERS

		Sulphuric acid (mg/m3)
		Zero	5	20
Analytical concentration		Not determined	5.7 ± 1.2	19.3 ± 4.0
Particle size (count median diameter ± geometric standard deviation)		0.4*	1.6 ± 2.6	2.4 ± 2.7
Percent of particles with a diameter of less than:
0.4		84.5	27.5	19.3
1.0		88.8	34.5	21.3
2.2		90.6	66.3	52.0
4.0		91.3	94.8	77.6
7.5		100.0	100.0	100.0
Total number of particle counts used to determine particle size		616,005	5,259,714	3,733,690
Relative humidity (%)**		44 ± 7	52 ± 5	56 ± 5
Temperature (°C)**		22 ± 1	22 ± 1	21 ± 1
*	This figure represents the airborne dust in the chamber
**	Mean ± standard deviation

Applicant's summary and conclusion

Conclusions:

Although slight maternal toxicity was seen at 20 mg/m3, little evidence of embryotoxicity was observed in mice exposed to 5 mg/m3 or 20 mg/m3 sulphuric acid for 7 h per day and a teratogenic effect was not detected.