Methacrylonitrile

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1985-07-29- 1986-02-12

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1986

Report date:

1986

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

observation period was 7 days.

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Methacrylonitrile

EC Number:

204-817-5

EC Name:

Methacrylonitrile

Cas Number:

126-98-7

Molecular formula:

C4H5N

IUPAC Name:

2-methylprop-2-enenitrile

Constituent 2

Reference substance name:

2-methyl-2-propenenitrile

IUPAC Name:

2-methyl-2-propenenitrile

Details on test material:

- Physical state: Colorless liquid with cyanogen-like odour
- Lot/batch No.: 507-03-004B
- Source: supplied by Asahi Chemical Industry Co Ltd
- Storage condition of test material: in closed vessel at cold dark place

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Japan SLC, Inc.
- Age at study initiation: 5 weeks
- Weight at study initiation: 87-108 g

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 2 degrees Centigrade
- Humidity: 55 ± 15 %
- Air changes (per hr): ventilated (all fresh air system) 15 times per hour
- Photoperiod (hrs dark / hrs light): 12-hour light-dark cycle (light on 8:00-20:00)

Administration / exposure

Type of coverage:

occlusive

Vehicle:

other: vehicle: 1%(v/v) Tween 80 in distilled water

Details on dermal exposure:

TEST SITE
- Area of exposure: back
- % coverage: 4 × 5 cm
- Type of wrap if used: Poly vinylidene chloride(PVDC) film for food use

REMOVAL OF TEST SUBSTANCE
- Washing: lukewarm water
- Time after start of exposure: 24 hr

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 10 mL/kg bodyweight
- Concentration (if solution): 0.5, 0.6, 0.8, 1.0, 1.2, 1.5, 1.9 mL/kg bodyweight
- Constant volume or concentration used: yes

VEHICLE
- Lot/batch no. (if required): ALE1780, Wako Pure Chemical Industries, Ltd. (Japan)

Duration of exposure:

24 hrs

Doses:

0.5, 0.6, 0.8, 1.0, 1.2, 1.5, 1.9 mL/kg bodyweight

No. of animals per sex per dose:

Seven female animals per dose level

Control animals:

no

Details on study design:

- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

Probit method

Results and discussion

Preliminary study:

No data

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

1.32 mL/kg bw

Based on:

test mat.

95% CL:

1.02 - 1.7

Mortality:

0.5 mL/kg: 0.0%
0.6 mL/kg: 0.0%
0.8 mL/kg: 14.3%
1.0 mL/kg: 28.6%
1.2 mL/kg: 57.1%
1.5 mL/kg: 42.9%
1.9 mL/kg: 100.0 %

Clinical signs:

other: Main signs: Day 0: decrease in locomotor activity, ptosis, dyspnea, hypothermia, sadation, straub tail Day 1: none of the signs described above

Gross pathology:

Dead animals: lung hemorrhage, subdural hemorrhage, slight erythema at the patch site
Survivors: no abnormalities

Other findings:

Cause of death was considered to be poisoning with hydrocyanic acid produced from the test substance in the body

Applicant's summary and conclusion

Conclusions:

LD50 was reported as 1.32 mL/kg bw in female rats