2-hydroxy-4-(methylthio)butyronitrile

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

24 november 1982 To 2 february 1983

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1983

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-hydroxy-4-(methylthio)butyronitrile

EC Number:

241-756-3

EC Name:

2-hydroxy-4-(methylthio)butyronitrile

Cas Number:

17773-41-0

Molecular formula:

C5H9NOS

IUPAC Name:

2-hydroxy-4-(methylsulfanyl)butanenitrile

Details on test material:

- Name of test material (as cited in study report): MMP-cyanhydrin
- Physical state: yellow clear liquid
- Analytical purity: no data
- Purity test date: no data
- Lot/batch No.: no data
- Expiration date of the lot/batch: no data
- Stability under test conditions: no data
- Storage condition of test material: no data

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Central institut for breeding of laboratory animals TNO, Zeist, The Netherlands.
- Age at study initiation: no data
- Weight at study initiation: males: 169 g (mean); females: 138g (mean)
- Fasting period before study: no data
- Housing: 5 to a cage
- Diet : ad libitum (Institut stock diet for rats)
- Water : ad libitum (bottled unfluorited tap-water)
- Acclimation period: no data


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/- 1
- Humidity (%): 50-60
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data


IN-LIFE DATES: From: 24 november 1983 To: 2 february 1983

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: glass cylinder (0.90 x 0.15 m)
- Exposure chamber volume: ca. 16 l
- Method of holding animals in test chamber: not restrained (the cylinder was fitted with an interior of perforated stainless stell plate for individual housing of the animals.
- Source and rate of air: The total air-flow through the cylinder was 12l/min.
- System of generating the test atmosphere: MMP-cyanhydrin was evaporated by passing a filtered and dried nitrogen flow through a glass evaporator filled with MMP-cyanhdrin and kept at 60 degrees centigrade. The nitrogen flow laden with MMP-cyanhydrin was mixed with filtered air from the compressed air line to provide the concentration desired.
- Treatment of exhaust air:
- Temperature, humidity, pressure in air chamber:


TEST ATMOSPHERE
- Brief description of analytical method used:
Nominal concentration: The nominal concentration was calculated by deviding the total quantity of the test material used by the total quantity of air which had been through the inhalation chamber during the exposure period.
Actual concentration : The actual concentration was calculated from determinations of MMP-cyanhydrin in air sampes. Samples were taken from the atmosphere by means of an air sampler, which was filled with 0.1 N NaOH, 45, 105, 165 and 225 minutes after the start of the exposure.
- Samples taken from breathing zone: yes

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

Nominal concentration: 938, 1111, 1979, 1 424, 930, 1100, 1940 mg/m3 air
Actual cncentration: 480 (390-600), 598 (400-990), 560 (490-670), 576 (516-612), 720 (660-800), 665 (540-780), 785 (640-1040) mg/m3 air

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: During the exposure and the observation period the rats were controlled for reactions to treatment daily. Body weighs were recorded just prior to exposure and at day 1, 2, 4, 7 and 14.
- Necropsy of survivors performed: yes (gross pathological examination)

Statistics:

No statistics were performed.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

651 mg/m³ air (analytical)

95% CL:

598 - 709

Exp. duration:

4 h

Mortality:

The animal that died, invariably died within a period of 30 hours after the start of the exposure, but far the most of the animals died during the exposure period. (See Table 1)

Clinical signs:

other: During the exposure period the animals, exposed to levels lower than 665 mg/m3 air, were lying with their eyes closed, but the animals of the 665, 720 and 785 mg/m3 groups had their eyes open and showed laboured respiration. After about 3 hours of exposur

Body weight:

Most males lost body weight during the first 1é hours after termination of the exposure, except for males of the 480 mg/m3 group. female lost body weight or gained hardly weight. After the second day both males and females gained weight in a normal way.

Gross pathology:

Gross examination at necropsy of the animals that died during the exposure revealed red areas on the lungs with a diameter of about 3 mm. this finding, however, is frequenly encountered in animals found dead. Other abnormalities were not observed in any these animals. Survivors, which were killed after the two week observation period did not show gross abnormalities.

Other findings:

no data

Any other information on results incl. tables

Table 1: Mean actual cncentrations of MMP-cyanhydrin and the corresponding mortality data

Mean actual concentration of MMP-cyanhydrin	number of death			Total death %
	at the end of exposure	at the end of day 0	at the end of day 1
480	0	0	0	0
598	0	0	0	0
560	1	1	1	10
576	3	3	3	30
720	2	4	6	60
665	4	7	8	80
785	5	7	10	100

Applicant's summary and conclusion

Interpretation of results:

other: category 2

Remarks:

Criteria used for interpretation of results: other: CLP

Conclusions:

Under the conditions of this test, the LC50 of MMP-cyanhydrin was 651 mg/m3 air (0.651 mg/l) when rats were exposed whole-body to a vapor of te test article for a single 4-hour period.

Executive summary:

During an acute inhalation toxicity study (similar to OECD TG 403) with MMP-cyanhydrin in Wistar rats, groups of male and female rats were to be exposed one single time for a period of four hours to an atmosphere containing a concentration of MMP-cyanhydrin, in order to determine the LC50. MMP-cyanydrin was administered to rats via whole-body vapor exposure at actual concentrations of 480, 598, 560, 576, 720, 665 and 785 mg/m3. during the exposure and the observation period the rats were controlled for reactions to treatment daily. Body weights were recorded just prior to exposure and at days 1, 2, 4, 7 and 14. At the end of the observation period all survivors were killed. Gross pathological examination was performed on all exposed rats. The animal that died, invariably died within a period of 30 hours after the start of the exposure, but far the most of the animals died during the exposure period. Mortality was 0/10, 0/10, 1/10, 3/10, 6/10, 8/10 and 10/10 animals for the 480, 598, 560, 576, 720, 665, 785 mg/m3 groups, respectively. During the exposure period the animals, exposed to levels lower than 665 mg/m3 air, were lying with their eyes closed, but the animals of the 665, 720 and 785 mg/m3 groups had their eyes open and showed laboured respiration. After about 3 hours of exposure convulsions occurred in all groups, but degree and frequency were much higher in animals of the 665, 720 and 785 mg/m3 groups. Twelve hours after termination of the exposure all surviving animals were completely recovered. Most males lost body weight during the first 1é hours after termination of the exposure, except for males of the 480 mg/m3 group. Female lost body weight or gained hardly weight. After the second day both males and females gained weight in a normal way. Gross examination at necropsy of the animals that died during the exposure revealed red areas on the lungs with a diameter of about 3 mm. this finding, however, is frequenly encountered in animals found dead. Other abnormalities were not observed in any these animals. Survivors, which were killed after the two week observation period did not show gross abnormalities. The results of the present acute inhalation toxicity study in rats showed that the 4 hour LC50 of MMP-cyanhydrin is 651 mg/m3 air. Under the conditions of this test, MMP-cyanhydrin is therfore classified as toxic according to Directive 67/548/EEC and category 2 according to CLP (GHS classification).