Hydrogen sulphide

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Concentration-time interactions in hydrogen sulfide toxicity in rats

Author:

Prior MG, Sharma AK, Yong S et al.

Year:

1988

Bibliographic source:

Can. J. Vet. Res. 52: 375-379

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Hydrogen sulphide

EC Number:

231-977-3

EC Name:

Hydrogen sulphide

Cas Number:

7783-06-4

Molecular formula:

H2S

IUPAC Name:

hydrogen sulfide

Details on test material:

Source: Matheson Gas Products, Edmonton, Alberta
Purity: 99.5%

Test animals

Species:

rat

Strain:

other: Long Evans, Sprague Dawley, and Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Inc., St. Constant, Quebec
- Age at study initiation: no data
- Weight at study initiation: recorded
- Housing: individually in stainless steel mesh cages
- Diet (ad libitum): certified laboratory rodent feed (Purina Laboratory Rodentb Chow5002)
- Water (ad libitum): reverse osmosis water
- Acclimation period: 10 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): 50 +/- 20
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

inhalation: gas

Type of inhalation exposure:

whole body

Details on inhalation exposure:

The exposure chambers were constructed of a clear, acrylic cylinder, with two removable stainless steel cones, and had a volume of 69.3 ± 0.2 L. Each chamber held three circular stainless steel mesh cages, holding four rats per cage in individual compartments. Flows of hydrogen sulphide and air were adjusted to maintain the target concentration in the inhalation chambers. Exhaust air from the chambers was passed through a portable fume scrubber (Mystaire, Plainview, New York) containing a 6% sodium hypochlorite solution, before release into the atmosphere.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

Hydrogen sulfide concentrations were monitored by gas chromatography four times per hour

Remarks on duration:

2, 4 or 6 hours

No. of animals per sex per dose:

9-12

Control animals:

yes

Details on study design:

Rats were assigned randomly to exposure groups, which were distributed randomly within the chambers. Seventy-two males and 84 females were assigned to the 2 and 6 h exposure groups, and 72 males and 72 females to the 4 h exposure groups, and exposed to various concentrations of hydrogen sulphide. Postmortem examinations were carried out on all animais dying during the exposure or during the 14 day postexposure observation period.

Statistics:

Standard regression and analysis of covariance techniques were used to estimate the effects of hydrogen sulphide concentration, sex, hours of exposure and strain on the weight loss of animals. Lethal concentration (LC10 and LC50) values were estimated by probit analysis using a maximum likelihood iteration technique. Hydrogen sulphide concentrations were transformed to the 1og10 scale for the analysis. Additional statistics on the standard deviation of the estimate, 95% confidence intervals, and the chi-square goodness of fit were also estimated

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LC50

Effect level:

587 ppm

Exp. duration:

2 h

Remarks on result:

other: = 821 mg/m3, no strain differences were observed

Effect levels 2

Sex:

male/female

Dose descriptor:

LC50

Effect level:

501 ppm

95% CL:

477 - 545

Exp. duration:

4 h

Remarks on result:

other: = 701 mg/m3, no strain differences were observed

Effect levels 3

Sex:

male/female

Dose descriptor:

LC50

Effect level:

335 ppm

95% CL:

325 - 345

Exp. duration:

6 h

Remarks on result:

other: = 469 mg/m3, no strain differences were observed

Mortality:

The probit equations of mortality in rats of all strains exposed to various concentrations of hydrogen sulphide for 2, 4 or 6 h is given in Table I.

Body weight:

The regression equation of hydrogen sulphide concentration on weight loss (Table II) showed a significant decrease in weight due to toxic gas concentration. For every 10 ppm (14 mg m-3) increase in gas concentration, the weight loss increased by 0.21 g in the pooled data.

Gross pathology:

The mouths and noses of all animals dying from hydrogen sulphide exposure contained considerable amounts of foamy fluid. The lungs failed to collapse when the thorax was opened and had severe pulmonary edema. The trachea and bronchi also contained large amounts of foamy fluid. Histological examination of the affected lungs revealed considerable amounts of proteinaceous fluid in the conductive airways, alveoli, and around the perivascular space of major blood vessels. These lesions were extensive enough to account for death.

Other findings:

The mean hydrogen sulphide concentration was almost identical at all 12 sampling positions, indicating a uniform flow and distribution of hydrogen sulphide within the chamber.

Any other information on results incl. tables

TABLE I. Probit Analysis of the Log₁₀Hydrogen Sulphide Concentration

		Standard	LCIo values	LC50values
DataSet	ProbitEquation	Deviation	Cl^a<LC10<Ch^b	Cl^a<LC50<Ch^b	x^2
Pooled	-5.7479 ± 3.8259X	0.2613	49<298<378	508<644<3743	192.81
2 h	-118.3300 ± 44.5478X	0.0224	^c-<549<597	^c-<587<-^c	78.96^d
4 h	-41.6105 ± 17.2645X	0.0579	364<422<447	477<501<545	19.16
6 h	-62.4003±26.6980X	0.0374	284<299<309	325<335<345	3.28
LE	-6.2369±4.0157X	0.2490	18<301<385	491<628<10086	73.04^d
SD	-2.8743 ± 2.7597X	0.3623	^c-<244<362	493<713<-^c	85.69^d
F344	-9.4625 ± 5.1946X	0.1925	60<344<422	499<608<33 17	86.18^d
Male	-3.5296 ± 3.0565X	0.3271	^c-<235<357	433<617<-^c	90.08^d
Female	-9.6517 ±5.2194X	0.1915	0<364<-^c	506<641<-^c	108.25^d

^aLower limit of 95% confidence interval

^bHigher limit of 95% confidence interval^'

^cNonestimable confidence interval values

^d(P < 0.01) forx²test of goodness to fit

TABLE II. Effect of Hydrogen Sulphide Concentration on Weight Loss of Animals

Group	n	Intercept	Slope ± Standard Error	Mean Standard Error	% Coefficient of Determination
Pooled	456	-21.632	0.0219^'± 0.0022	5.60	17.89
2 h	156	-21.564	0.0240^'± 0.0048	3.53	13.89
4 h	144	-26.034	0.0279' ± 0.0070	5.27	10.11
6h	156	-13.282	0.0063±0.0097	6.88	0.27

^aHighly significant (P < 0.01)

Applicant's summary and conclusion

Executive summary:

Groups of male and female Long Evans, Sprague Dawley, and Fischer 344 rats were exposed to varying concentrations of hydrogen sulfide for 2, 4, or 6 hours, followed by a 14-day observation period. Exposure chambers were clear, acrylic horizontal flow chambers with two removable stainless steel cones with a total volume of 69 liters. Hydrogen sulfide concentrations were monitored by gas chromatography four times per hour. LC50 values of 587, 501, and 335 ppm were calculated for the 2, 4, and 6 hr time points, respectively. No strain differences were observed.