1,2,3,6-tetrahydromethyl-3,6-methanophthalic anhydride

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: Experimental data with study designed according to standard methods

Data source

Reference

Reference Type:

grey literature

Title:

Unnamed

Year:

1981

Report date:

1981

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

1,2,3,6-tetrahydromethyl-3,6-methanophthalic anhydride

EC Number:

246-644-8

EC Name:

1,2,3,6-tetrahydromethyl-3,6-methanophthalic anhydride

Cas Number:

25134-21-8

Molecular formula:

C10H10O3

IUPAC Name:

3a,4,7,7a-tetrahydromethyl-4,7-methano-2-benzofuran-1,3-dione

Details on test material:

- Name of test material (as cited in study report): Nadic methyl anhydride
- Physical state: Liquid

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

No data
TEST ANIMALS
- Source: Blue Spruce Farms Inc.
- Fasting period before study: None
- Housing: During acclimatisation group caged, 5 same sex/cage. During study Individually caged in wire mesh cages
- Diet (e.g. ad libitum): ad libitum except during 4 hour exposure period
- Water (e.g. ad libitum): ad libitum except during 4 hour exposure period
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS - No data

IN-LIFE DATES: From: 1981-2-12 To: 1981-2-26

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

whole body

Vehicle:

other: ethanol

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Stainless steel and glass cylindrical chamber
- Exposure chamber volume: 361 L
- Method of holding animals in test chamber: Whole body exposure with animals in wire mesh cages within exposure chamber
- Source and rate of air: Room air drawn into chamber by Vortex transvector jet at flow rate of 70 L/minute
- Method of conditioning air: Not applicable
- System of generating particulates/aerosols: Fluid metering pump feeding an atomiser
- Method of particle size determination: Cascade impactor
- Treatment of exhaust air: Vented to extraction hood
- Temperature, humidity, pressure in air chamber: 21-22 deg C; 41-57% RH; no data on pressure

TEST ATMOSPHERE
- Brief description of analytical method used: Gravimetric analysis - 5L of chamber air drawn through glass fibre filter. Weight of trapped material used to calculate chamber concentration. Samples taken twice/hour and time weighted average concentration calculated for the 4 hour exposure period
- Samples taken from breathing zone: yes

VEHICLE
- Composition of vehicle (if applicable): Ethanol
- Concentration of test material in vehicle (if applicable): 90% w/w
- Justification of choice of vehicle: No data

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: Particles <10 micron - 93%
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 3.2 / 2.1 micron

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

Nominal - 4.9 mg/L
Achieved - 0.75 mg/L

No. of animals per sex per dose:

5 males / 5 female

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations at intervals on day of exposure and daily thereafter. Body weight recorded Prior to exposure (Day 1) and on Days 3, 4, 5, 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: Whole head with nasal passages, trachea, bronchi, lungs, liver and kidneys preserved in buffed formalin

Statistics:

No data

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LC50

Effect level:

< 4.9 mg/L air (nominal)

Based on:

test mat.

Exp. duration:

4 h

Effect levels 2

Sex:

male/female

Dose descriptor:

LC50

Effect level:

< 0.75 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

3/5 males and 5/5 females

Clinical signs:

other: Laboured breathing, nasal discharge and wet coat noted in all animals during exposure. Urinary incontinence, bloody urine, bloody discharge around ano-genital region and film covered appearance of eyes seen in individual animals following exposure.

Body weight:

Weight loss occurred in all animals following exposure. Only 1 of the 2 surviving animals re-gained its original body weight.

Gross pathology:

No unusual findings

Applicant's summary and conclusion

Interpretation of results:

toxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Acute toxicity has been determined in the rat following 4 hours inhalation exposure. A single group of rats were exposed to a nominal concentration of 4.9 mg/L (achieved concentration was 0.75 mg/L) and 80% mortality occurred. The median lethal concentration (LC50) is therefore less than the concentration investigated.

Executive summary:

Acute toxicity has been determined in the rat following 4 hours inhalation exposure. A single group of rats were exposed to a nominal concentration of 4.9 mg/L (achieved concentration was 0.75 mg/L) and 80% mortality occurred. The median lethal concentration (LC50) is therefore less than the concentration investigated.