Reaction mass of sulphuric acid, hydrogen peroxide and peroxomonosulphuric acid

Toxicity to reproduction

Administrative data

Endpoint:

toxicity to reproduction

Remarks:

other: prenatal developmental toxicity study

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:

other: 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:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Nulliparous New Zealand White rabbits (Langshaws Rabbitry, Augusta, 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.
- Rabbits were acclimated to the environment for at least three 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)

Details on mating procedure:

- Female rabbits were artificially inseminated.
- The day on which artificial insemination took place in rabbits was considered to be day zero of gestation.

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.

Duration of treatment / exposure:

- Day 6 to day 18 of gestation.

Frequency of treatment:

- Exposure took place for 7 h per day

Details on study schedule:

- Rabbits were sacrificed by carbon dioxide inhalation on day 29 of gestation.

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0 mg/m³ air (nominal)

Doses / concentrations 2

Dose / conc.:

5 mg/m³ air (nominal)

Doses / concentrations 3

Dose / conc.:

20 mg/m³ air (nominal)

No. of animals per sex per dose:

- 20 bred rabbits were exposed in each group.
- Twenty bred rabbits acted as vehicle controls and were exposed to filtered room air.

Control animals:

yes, sham-exposed

Examinations

Parental animals: Observations and examinations:

- All animals were observed daily beginning on day 6 of gestation for indications of toxicity.
- Body weights were recorded on days 6, 9, 12, 15, 19 and 29 of gestation.

Litter observations:

- The number and position of live, dead and resorbed foetuses was noted.

Postmortem examinations (parental animals):

- The maternal liver was weighed.
- Respiratory tract tissues from 6 dams in each group were preserved in formalin and examined histologically.
- The nasal turbinates were decalcified and a section taken through a transverse plane.
- A minimum of 6 lung sections and a transverse section of trachea were taken from each rabbit.
- The tissues were processed by routine histologic procedures and stained with hematoxyylin and eosin prior to light microscopy.
- The uterus of each non-pregnant female was stained with a 10 % solution of sodium sulphide and examined for evidence of implantation sites.

Postmortem examinations (offspring):

- 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.

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:

no effects observed

Description (incidence and severity):

inhalation of 5 mg/m3 or 20 mg/m3 of sulphuric acid did not alter the appearance of dams

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

statistically significant decrease in maternal body weight gain was noted during the first few days of exposure to 20 mg/m3 sulphuric acid

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Description (incidence and severity):

statistically significant decrease in maternal body weight gain was noted during the first few days of exposure to 20 mg/m3 sulphuric acid

Organ weight findings including organ / body weight ratios:

no effects observed

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Description (incidence and severity):

a trend towards dose related increase in the incidence of subacute rhinitis and tracheitis was noted

Other effects:

not examined

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:

not examined

Reproductive function: sperm measures:

not examined

Reproductive performance:

no effects observed

Description (incidence and severity):

incidence of pregnancy and proportion of pregnancies detected by sodium sulphide stain was not significantly altered in comparison to the control group

Details on results (P0)

- One control rabbit delivered a litter on day 28 of gestation.
- One rabbit from the 5 mg/m3 group delivered a litter on day 26 of gestation.

Effect levels (P0)

1

Dose descriptor:

LOAEC

Effect level:

19.3 mg/m³ air (analytical)

Based on:

test mat.

Sex:

female

Basis for effect level:

body weight and weight gain

food consumption and compound intake

histopathology: non-neoplastic

2

Dose descriptor:

NOEC

Effect level:

5.7 mg/m³ air (analytical)

Based on:

test mat.

Sex:

female

Basis for effect level:

body weight and weight gain

food consumption and compound intake

histopathology: non-neoplastic

Results: F1 generation

General toxicity (F1)

Clinical signs:

not examined

Mortality / viability:

not examined

Body weight and weight changes:

not examined

Sexual maturation:

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

not examined

Histopathological findings:

not examined

Details on results (F1)

- The mean numbers of implants per dam, live foetuses per litter, or resorptions per litter were not significantly altered by exposure.
- No significant effect on foetal sex ratio was seen,
- Mean weights and lengths of offspring were not significantly altered from their respective control values.

Effect levels (F1)

Generation:

F1

Remarks on result:

not determinable due to absence of adverse toxic effects

Overall reproductive toxicity

Reproductive 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 when rabbits were exposed to 20 mg/m3 sulphuric acid, no other evidence of reproductive toxicity was noted under the conditions of the investigation.