Chlorosulphuric acid

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

The data is from peer reviewed publication

Data source

Reference

Reference Type:

publication

Title:

Repeated dose oral toxicity study of the test chemical

Author:

Upton and L'Estrange

Year:

1977

Bibliographic source:

Quarterly Journal of Experimental Physiology

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)

Principles of method if other than guideline:

The study was performed to evaluate the toxic effects of the test chemical in rats upon repeated exposure by oral route in 90 days study

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Hydrogen chloride

EC Number:

231-595-7

EC Name:

Hydrogen chloride

Cas Number:

7647-01-0

Molecular formula:

ClH

IUPAC Name:

hydrogen chloride

Test material form:

liquid

Details on test material:

- Name of test material : Hydrochloric Acid
- Molecular formula : ClH
- Molecular weight : 36.4609 g/mol
- Substance type: Inorganic
- Physical state: Liquid
- Impurities (identity and concentrations): No Data Available

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: No Data Available
- Age at study initiation: Approx. 1 year old
- Weight at study initiation: Approx. 350 grams
- Fasting period before study: No Data Available
- Housing: No Data Available
- Diet (e.g. ad libitum): Commercial rat diet ad libitum
- Water (e.g. ad libitum): Supplied daily ad libitum.
- Acclimation period: No Data Available.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): No Data Available
- Humidity (%): No Data Available
- Air changes (per hr): No Data Available
- Photoperiod (hrs dark / hrs light): No Data Available

Administration / exposure

Route of administration:

oral: feed

Vehicle:

other: Commercial Rat Diet

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS: The rats were offered the diet alone or supplemented with 312, 625, 937 or 1250 mmol/kg Dry matter. Batches of the diet were prepared using 125 ml of 2 5, 5-0, 7-5 or 10 0 mol /L solutions of HCl for the acid treatments respectively and 125 ml water for the control per kg basal diet. Each diet was offered ad libitum over a 9 week period to four male and four female rats in a randomized block design experiment.

DIET PREPARATION
- Rate of preparation of diet (frequency): No Data Available
- Mixing appropriate amounts with (Type of food): No Data Available
- Storage temperature of food: No Data Available.

VEHICLE
- Justification for use and choice of vehicle (if other than water): No Data Available
- Concentration in vehicle: 0, 312, 625, 937 or 1250 mmol/kg DM
- Amount of vehicle (if gavage): 0, 2.5, 5.0, 7.5 or 10.0 mol/L.
- Lot/batch no. (if required): No Data Available
- Purity: No Data Available

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

No Data Available

Duration of treatment / exposure:

7 weeks

Frequency of treatment:

Daily

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0 other: mmol/ kg dry matter

Doses / concentrations 2

Dose / conc.:

312 other: mmol/kg dry matter

Doses / concentrations 3

Dose / conc.:

625 other: mmol/kg dry matter

Doses / concentrations 4

Dose / conc.:

937 other: mmol/kg dry matter

Doses / concentrations 5

Dose / conc.:

1 250 other: mmol/kg dry matter

No. of animals per sex per dose:

No Data Available

Control animals:

yes, concurrent vehicle

Details on study design:

No Data Available

Positive control:

No Data Available

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: No Data Available
- Time schedule: No Data Available
- Cage side observations checked in table [No.?] were included.

DETAILED CLINICAL OBSERVATIONS: No Data Available
- Time schedule: No Data Available

BODY WEIGHT: Yes
- Time schedule for examinations: No Data Available

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes, residues were collected weekly and intake was calculated for weekly periods
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes, intake was calculated for weekly periods

FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes
- Time schedule for examinations: Intake was calculated for weekly periods

OPHTHALMOSCOPIC EXAMINATION: No data
- Time schedule for examinations: No Data Available
- Dose groups that were examined: No Data Available

HAEMATOLOGY: Yes
- Time schedule for collection of blood: At the end of the experiment
- Anaesthetic used for blood collection: Yes, blood was collected by cardiac puncture using anesthesia.
- Animals fasted: No data available
- How many animals: No Data Available
- Parameters checked in table [No.?] were examined: No Data Available

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: At the end of the experiment
- Animals fasted: No Data Available
- How many animals: No Data Available
- Parameters checked in table [No.?] were examined. acid-base and mineral analysis

URINALYSIS: No data available
- Time schedule for collection of urine: No Data Available
- Metabolism cages used for collection of urine: No Data Available
- Animals fasted: No Data Available
- Parameters checked in table [No.?] were examined.

NEUROBEHAVIOURAL EXAMINATION: No data available
- Time schedule for examinations: No Data Available
- Dose groups that were examined: No Data Available
- Battery of functions tested: No Data Available
sensory activity / grip strength / motor activity / other: No Data Available

Sacrifice and pathology:

Sacrifice: Rats were sacrificed using exsanguination.

GROSS PATHOLOGY: Yes, After exsanguination, the rats were slaughtered and the right femur was removed from each animal, cleansed of adherent soft tissue and dried at 100 'C. It was subjected to fat extraction by petroleum ether in a Soxhlet apparatus, dried at 100 'C, weighed and the weight was recorded as fat free solids (FFS). The FFS were ashed at 560 'C and dissolved in 2 mol/L 1 nitric acid for subsequent analysis.

HISTOPATHOLOGY: Yes

Other examinations:

No Data Available

Statistics:

Where treatment effects were statistically significant the means were compared with each other using Duncan's multiple range test.

Results and discussion

Results of examinations

Clinical signs:

not specified

Mortality:

mortality observed, treatment-related

Description (incidence):

100% mortality was observed at higher doses of 937 and 1250 mmol/kg. There was no mortality observed at 312 and 625 mmol/kg.

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

There was a significant reduction of the body weights of the animals in the higher dose groups of 937 and 1250 mmol/kg.

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Description (incidence and severity):

There was a significant decrease in the food intake of 937 and 1250 mmol/kg.

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

effects observed, treatment-related

Description (incidence and severity):

The water intake was significantly increased by the test chemical supplementation except on the high level of supplementation, where the animals survived for a short period.

Ophthalmological findings:

not specified

Haematological findings:

effects observed, treatment-related

Description (incidence and severity):

Blood pH was significantly reduced by the test chemical supplementation. Plasma CO2 concentration was also reduced by the test chemical supplementation but the effect was not significant.

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Effect levels

1

Dose descriptor:

NOAEL

Effect level:

625 other: mmol /kg

Based on:

test mat.

Sex:

male/female

Basis for effect level:

body weight and weight gain

food consumption and compound intake

haematology

mortality

water consumption and compound intake

2

Dose descriptor:

LOAEL

Effect level:

937 other: mmol /kg

Based on:

test mat.

Sex:

male/female

Basis for effect level:

body weight and weight gain

food consumption and compound intake

haematology

mortality

water consumption and compound intake

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Table: Live-wt. change, dry matter (DM) intake, blood and bone measurements for weanling rats given a balanced diet alone or supplemented with the test chemical at 3 different levels. (Mean of eight rats offered the diet ad lib. for 63 days).

	0	312	625	938	1250	SE of treatment mean	+F- test
pH of diets	5.80	4.17	2.84	2.23	1.82	-	-
Dm intake	14.8	15.8	15.3	10.7	9.56	0.38	***
Liver weight change (g/d)	-0.31	-0.22	-0.47	-2.40	-1.72	0.15	***
Water intake (mL/D)	33.9	35.7	44.8	44.2	25.9	1.47	***
Blood measurements
Blood pH	7.38`	7.29	7.29	-	-	0.025	*
Plasma CO2 (mmol/L)	23.4	22.7	20.7	-	-	1.95	NS
Bone measurements
Femur length (mm)	37.3	36.7	3838	-	-	0.64	NS
Wt. fat free solids (FFS) in femur (mg)	695	729	666	-	-	26.7	NS
% ash in FFS	70.8	61.3	69.4	-	-	3.39	NS
% Ca in FFS	23.7	24.7	23.2	-	-	0.49	NS
% P in FFS	12.4	12.6	13.0	-	-	0.39	NS

Applicant's summary and conclusion

Conclusions:

The no observed adverse effect level (NOAEL) and the low observed adverse effect level (LOAEL) for the test chemical after the administration for over 7 weeks to Wistar rats is considered to be 625 mmol /kg and 937 mmol /kg respectively.

Executive summary:

Repeated dose oral toxicity study was conducted to identify and evaluate effects of the test chemical on male and female Wistar rats for a period of 7 weeks. In this period, the rats were administered with the test chemical which was given through the oral feed route. The test chemical was mixed with the diet in concentrations of 2.5, 5.0, 7.5 or 10.0 mol/L and dose groups ofmmol /kg. The rats were given a commercial rat diet, either alone (control) or supplemented with the test chemical at 312, 625, 937 or 1250 mmol/ kg DM. The pH reached 1.82 after using higher dietary levels of the test chemical (i.e at 1250 mmol/kg). Batches of the diet were prepared by pouring 140 ml of either 2, 3 or 4 mol /l solutions of the test chemical for the acid treatments respectively over a kg D.M. of the experimental diet and mixed thoroughly in a food mixer. The control diet was prepared by the addition of a similar amount of distilled water to the basal diet. The rats were given access to the waterad libitum.The control animals were fed with animal diets mixed with distilled water. The rats were observed for body weight gain and feed consumption throughout the study.100% mortality was observed at higher doses of 937 and 1250 mmol/kg. There was no mortality observed at 312 and 625 mmol/kg. Also, there was a significant reduction of the body weights of the animals in the higher dose groups of 937 and 1250 mmol/kg. There was a significant decrease in the food intake of 937 and 1250 mmol/kg. The water intake was significantly increased by the test chemical supplementation except on the high level of supplementation, where the animals survived for a short period. After the administration of the test chemical for 7 weeks the animals were sacrificed by exsanguination and were slaughtered to isolate the femur bones of the animals. The blood was collected at the end of the experiment under the influence of anesthesia to evaluate blood acid status and CO2levels in the blood. Also, values of the minerals were determined. Blood pH was significantly reduced by the test chemical supplementation. Plasma CO2 concentration was also reduced by the test chemical supplementation but the effect was not significant. The supplementation of test chemical did not significantly cause any changes in the levels of calcium and phosphorus in the animals. Also, There were no gross pathological changes observed in the animals due to administration of the test chemical and There were no observed changes in histopathological examination after the administration of the test chemical. From all the observations, The no observed adverse effect level (NOAEL) and the low observed adverse effect level (LOAEL) for the test chemical after the administration for over 9 weeks to Wistar rats is considered to be 625 mmol /kg and 937 mmol /kg respectively.