2-hydroxy-2-methylpropionitrile

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: - Basic data given: comparable to guideline

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1981

Report date:

1981

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Principles of method if other than guideline:

Deviations from guideline: at least 5 animals of the same sex should be used at each dose level. 2 males and 2 females per group were used in this study.

GLP compliance:

no

Remarks:

Study performed before implementation of GLP

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-hydroxy-2-methylpropionitrile

EC Number:

200-909-4

EC Name:

2-hydroxy-2-methylpropionitrile

Cas Number:

75-86-5

Molecular formula:

C4H7NO

IUPAC Name:

2-hydroxy-2-methylpropanenitrile

Details on test material:

- Name of test material (as cited in study report): acteone cyanohydrin, also known as methyl lactonitrile or alpha-hydroxyisobutyronitrile
- Physical state: light amber liquid
- Typical analysis for the test item: acetone cyanohydrin wt %: 98.0; acetone wt %: 0.80, water wt %: 0.40, hydrogen cyanide wt %: 0.35 %, stabilizer and inert material wt %: 0.20; in total: 99.75 %

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Langshaw Farms, Augusta, Michigan, U.S.A.
- Age at study initiation: no data
- Weight at study initiation: male: 3280 - 3530 g, female: 3200 - 3490 g
- Fasting period before study: no data
- Housing: individual holding cages with free access to food and water
- Diet: ad libitum, commercial laboratory chow (Ralston Purina Company, St. Louis, Missouri, U.S.A)
- Water: ad libitum
- Acclimation period: 2 weeks


ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 h light and dark cycle

Administration / exposure

Type of coverage:

occlusive

Vehicle:

water

Details on dermal exposure:

TEST SITE
24 hours prior to application of the test item, the entire trunk of 2 male and 2 female rabbits/dose level was clipped free of hair with electric clipper.
- Area of exposure: trunk
- Type of wrap if used: heavy-gauge SARAN Film sleeve held in place with rubber bands. The plastic sleeve was covered by a cloth bandage taped securely to the marginal hair.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): skin was washed with a mild soap and water, rinsed thoroughly and dried with a soft disposable towel
- Time after start of exposure: after 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): unstated
- Concentration (if solution): 6, 25, 40 mg/kg
- Constant volume or concentration used: unstated

Duration of exposure:

24 h

Doses:

6, 25, 40 mg/kg of test item (10 % aq.)

No. of animals per sex per dose:

2 males and 2 females/ dose level

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: frequently, after 24 h observations for erythema, edema, necrosis
- Frequency of weighing: before and after the 24 h exposure, and at 1 and 2 weeks post-treatment
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,

Statistics:

The LD50 was calculated by the moving average method (Thompson and Weil, 1952). The approximate slope was calculated as 1/2 log10 (LD84/LD16) (Thompson, W.R. and C.S. Weil, Biometrics, Vol. 8, No. 1, March 1952, pp. 51-54

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

16 mg/kg bw

95% CL:

>= 8 - <= 28

Remarks on result:

other: estimation

Mortality:

6 mg/kg bw: 0/4 animals
25 mg/kg bw: 3/4 animals, 2 rabbits after 3 hours, 1 rabbit after 4 hours
40 mg/kg bw: 4/4 animals, 2 rabbits after 3 hours, 2 rabbits after 4 hours

Clinical signs:

other: 6 mg/kg bw: 4/4 animals after 2 h: lethargy 25 mg/kg bw: 4/4 animals after 1.5 h lethary; 2/4 animals after 1,5 h: labored breathing; 1/4 animals after 3 h: convulsions 40 mg/kg bw: 4/4 animals after 1 h: lethargy; 3/4 animals (2 rabbits after 1 h, 1 rabb

Gross pathology:

No evidence of either external or internal lesions considered to be treatment-related.

Applicant's summary and conclusion

Interpretation of results:

Category 1 based on GHS criteria

Remarks:

Migrated information

Conclusions:

Legally binding harmonised classification as given in REGULATION (EC) No 1272/2008 Annex VI Table 3.1 (GHS): Acute tox. 1; H310 and Table 3.2 (Annex I of Directive 67/548/EEC): T+; R26/27/28.

Executive summary:

In an acute dermal toxicity study equivalent to OECD TG 402 (1981) 3 groups of New Zealand White rabbits (2 males and 2 females per dose level) were dermally exposed to Acetone Cyanohydrin (98 wt % a.i., 10 % aq.) for 24 hours at doses of 6, 25, 40 mg/kg bw. Animals then were observed for 14 days.

Dermal LD₅₀ Combined = 16 mg/kg bw (95% C.I. 8 - 28)

Lethargy (at 6, 25, 40 mg/kg bw), labored breathing (at 25 and 40 mg/kg bw), and convulsions (at 25 mg/kg bw) were clinical signs of toxicity observed after treatment. There were no treatment related necropsy findings. Slight (4/5 animals) to moderate (1/5 animals) redness, slight swelling in 3/5 animals, and slight necrosis in 1/5 animals were found after 24 hours post treatment in the surviving animals.

Legally binding harmonised classification as given in REGULATION (EC) No 1272/2008 Annex VI Table 3.1 (GHS):

Acute tox. 1; H310 and Table 3.2 (Annex I of Directive 67/548/EEC): T+; R26/27/28.

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