Propiononitrile

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

3rd December 1981 - 17th December 1981

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1981

Report date:

1981

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

not specified

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: 40 CFR Part 163.81-2 - US EPA, Pesticides Programs. Proposed Guidelines for Registering Pesticides in the US; Hazard Evaluation: Humans and Domestic Animals. Acute Dermal Toxicity Study.

Deviations:

not specified

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Propiononitrile

EC Number:

203-464-4

EC Name:

Propiononitrile

Cas Number:

107-12-0

Molecular formula:

C3H5N

IUPAC Name:

propanenitrile

Test material form:

liquid

Specific details on test material used for the study:

Appearance: Dark amber liquid.
Density: 0.7986 g/mL.
Storage: Room temperature.

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

Young adult rabbits, weighing 2-4 kg, allowed to acclimatise for minimum 2 weeks. Animals were housed in individual cages with temperature being maintained between 15.5-21°C, and 12-hour light-dark cycle. Water and food were provided ad libitum. Body weight was monitored: pre-test at the time of clipping (which were used in dose calculation), day 7 and 14, and at the time of death.

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

The hair of each rabbit clipped from the trunk with an electrical clipper exposing minimum 20% of the body surface area, ensuring the skin remaining intact. The test substance was directly applied onto the exposed skin, ensuring even application. A gauze was then wrapped around, covering the exposure site securing with a tape.

Duration of exposure:

Single 24-hour application followed by 14 days observation period.

Doses:

12.5, 25, 50 and 100 mg/kg bw.

No. of animals per sex per dose:

5

Control animals:

yes, concurrent no treatment

Statistics:

95 % Confidence limits

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

43 mg/kg bw

Based on:

test mat.

95% CL:

>= 24 - <= 62

Effect levels 2

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

35 mg/kg bw

Based on:

test mat.

Mortality:

Four out of five females and five out of five males died following 3-23 hours exposure to 50 mg/kg bw of the test substance. All animals died following 2-7 hours of exposure to 100 mg/kg bw of the test substance.

Clinical signs:

other: Animals prior to death exhibited the following signs of toxicity, including: ataxia, convulsions, tremors, respiratory abnormalities (hyperpnoea, hypopnea, dyspnoea and arrhythmic respiration), hypoactivity, prostration, hypothermia, a few animals showed

Gross pathology:

Post-mortem observations revealed that animals exposed to 50 or 100 mg/kg bw of test material showed reddening of the nictitating membrane, mottling of the liver and numerous gastric abnormalities (reddened walls, black foci in the mucosa, black material adhered to the mucosa), and red intestinal walls or intestinal contents. Necropsy observations revealed at the dose of 12.5 mg/kg on one instance pericardial sac filled with fluid. Lungs appeared pale red at every dose, except for 100 mg/kg, in some instances dark red/brown foci and/or bright red dots were observed. Gall bladder appeared small in one or two animals treated with 12.5 and 25 mg/kg of substance. In some instances, spleen appeared small, pitted, irregular, roughened and mottled purple. Kidneys appeared mottled pale (two instances, at 12.5 and 25 mg/kg) and pitted in one instances at a of dose 25 mg/kg, as well as dark red depressions seeing at 100 mg/kg dose. Adrenals appeared mottled dark red at 25 and 100 mg/kg dose, with red foci seeing only with high deses (50 and 100 mg/kg bw). At a dose of 12.5 mg/kg bw ovaries had clear cysts in one female and had a red appearance in one other female. Uterus appeared pale on three instances, at 12.5, 25 and 50 mg/kg bw, redness was observed more commonly at the higher dose (100 mg/kg bw) in 4 out of five females. Observations in animals killed after 14 days were generally similar to observations seen in control rabbits in this laboratory.

Other findings:

Dermal observations: Animals surviving at 24 hours exhibited little or no dermal response. Six out of ten animals at the 12.5 mg/kg dose and three out of ten animals at 25 mg/kg dose showed no dermal irritation, while the remaining animals showed only slight or very slight erythema with no oedema.

Any other information on results incl. tables

Mortality.

Dose (mg/kg)	Male mortality (number/total)	Female mortality (number/total)	Total mortality (number/total)	Time of death (h)
12.5	0/5	0/5	0/10	-
25	0/5	0/5	0/10	-
50	4/5	5/5	9/10	3 -23
100	5/5	5/5	10/10	2 -7.5
LD50 (mg/kg)	43	35	40
95% Confidence limits (mg/kg)	24 -62	Cannot be calculated	29 -51

Applicant's summary and conclusion

Interpretation of results:

Category 1 based on GHS criteria

Conclusions:

The dermal LD50 was 43 and 35 mg/kg bw for males and females, respectively. The test substance has been classified as category 1 acute dermal toxicity.

Executive summary:

The substance was used in a reliable in vivo acute dermal toxicity study using male and female rabbits (n = 5/sex). The animals were exposed to 12.5, 25, 50 and 100 mg/kg bw of undiluted substance. The test substance was directly applied onto the exposed skin as a single 24-hour application and animals monitored for the period of 14 days. Following 3 -23 hours of exposure to 50 mg/kg bw four out of five males and five out five females died.

Following 2 -7.5 hours of exposure to 100 mg/kg bw of the test substance all animals died.

Animals surviving 24 hours following exposure exhibited little or no dermal response. Six out of ten animals at the 12.5 mg/kg bw dose and three out of ten animals at 25 mg/kg bw dose showed no dermal irritation, while the remaining animals showed only slight or very slight erythema with no oedema. The dermal LD50 was 43 and 35 mg/kg bw for males and females, respectively. The test substance has been classified as category 1 acute dermal toxicity.